Inhibitors of human immunodeficiency virus replication

Patent metadata

Field	Value
Publication number	US-2021393633-A1
Application number	US-201917284855-A
Country	US
Kind code	A1
Filing date	Oct 22, 2019
Priority date	Oct 25, 2018
Publication date	Dec 23, 2021
Grant date	—

Abstract

Compounds of Formula I, including pharmaceutically acceptable salts thereof, and compositions and methods for treating human immunodeficiency virus (HIV) infection are set forth:

First claim

1 . A compound of Formula I, or a pharmaceutically acceptable salt thereof:

wherein:
G 1 is C 6 -C 8 alkyl optionally substituted with 1-3 fluorines, or G 1 is C 2 -C 5 alkyl substituted with —(C 2 -C 3 alkylenyl)- and optionally substituted once with G 2 and optionally substituted with 1-3 fluorines, or G 1 is C 1 -C 5 alkyl substituted with G 2 , or G 1 is one of the following:

Z 1 and Z 3 are independently —C 1 -C 3 alkylene optionally substituted once with —CH 3 or —CH 2 CH 3 ;
Z 2 is —O—, —S(O 2 )—, —NH—, or —N(G 4 );
X 1 , X 2 , and X 3 are independently H, F, or Cl, wherein one of X 1 , X 2 , and X 3 may optionally be selected from —CN, —OCH 3 , —CH 3 , —CH 2 F, —CHF 2 , and —CF 3 ;
E 4 and E 5 are independently —C 1 -C 2 alkylene optionally substituted once with —CH 3 , or —CH 2 CH 3 ;
E 6 is —C(H 2 )—, —O—, —S(O 2 )—, —NH—, or —N(G 4 );
E 7 , E 8 , and E 9 are independently H or —CH 3;
Y 1 and Y 2 are independently —N(H)— or —O—;
G 2 is phenyl, —OH, —O(C 1 -C 3 alkyl) optionally substituted with 1-3 fluorines, C 3 -C 4 cycloalkyl optionally substituted with 1-2 fluorines, or G 2 is the following:

G 4 is C 1 -C 2 alkyl optionally substituted with 1-3 fluorines, or C 3 -C 4 cycloalkyl optionally substituted with 1-2 fluorines;
R 1 is hydrogen, C 1 -C 3 alkyl optionally substituted with 1-3 fluorines, or C 1 -C 3 cycloalkyl optionally substituted with 1-3 fluorines;
R 2 is C 1 -C 6 alkyl optionally substituted with 1-3 fluorines, or C 3 -C 6 cycloalkyl optionally substituted with 1-3 fluorines;
R 3 is hydrogen, Cl, F, CH 3 , or OCH 3 ;
W is selected from:

2 . A compound or salt according to claim 1 wherein W is the following:

3 . A compound or salt according to claim 1 wherein W is the following:

4 . A compound or salt according to claim 1 wherein R 1 is —CH 3 , —CH 2 CHF 2 , or —CH 2 CF 3 ; R 2 is —CH 3 or cyclopropyl; and R 3 is H, Cl or CH 3 .

5 . A compound or salt according to claim 1 wherein R 1 is —CH 3 ; R 2 is —CH 3 ; and R 3 is Cl.

6 . A compound or salt according to claim 1 wherein X 1 , X 2 , and X 3 are independently H or F.

7 . A compound or salt according to claim 1 wherein X 1 is F, X 2 is H, and X 3 is F.

8 . A compound or salt according to claim 1 wherein G 1 is C 6 -C 8 alkyl optionally substituted with 1-3 fluorines.

9 . A compound or salt according to claim 1 wherein G 1 is C 2 -C 5 alkyl substituted with -(C 2 -C 3 alkylenyl)- and optionally substituted once with G 2 and optionally substituted with 1-3 fluorines.

10 . A compound or salt according to claim 1 wherein G 1 is:

11 . A compound or salt according to claim 1 wherein G 1 is:

12 . A compound or salt according to claim 1 wherein G 1 is:

13 . A compound or salt according to claim 1 wherein G 1 is:

14 . A compound or salt according to claim 1 wherein G 1 is one of the following:

15 . A compound or salt according to claim 1 wherein G 1 contains a fluorine atom.

16 . A compound or salt according to claim 1 wherein the stereochemistry is as denicted below:

17 . A compound or salt according to claim 1 wherein the stereochemistry is as depicted below:

18 . A compound or salt according to claim 1 , selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

19 . A compound or salt according to claim 1 , selected from the group consisting of:

and pharmaceutically acceptable salts thereof.

20 . A pharmaceutical composition comprising a compound or salt according to claim 1 .

21 . A composition according to claim 20 further comprising a pharmaceutically acceptable carrier, excipient, and/or diluent.

22 . A method of treating HIV infection comprising administering a composition according to claim 20 to a patient.

23 . The method of claim 22 wherein said administration is oral.

24 . The method of claim 22 wherein said administration is by injection intramuscularly or subcutaneously.

25 . The method of claim 22 , wherein said method further comprises administration of at least one other agent used for treatment of AIDS or HIV infection selected from the group consisting of nucleoside HIV reverse transcriptase inhibitors, non-nucleoside HIV reverse transcriptase inhibitors, HIV protease inhibitors, HIV fusion inhibitors, HIV attachment inhibitors, CCR5 inhibitors, CXCR4 inhibitors, HIV budding or maturation inhibitors, and HIV integrase inhibitors.

26 - 29 (canceled)

Assignees

• Viiv Healthcare Uk No 5 Ltd

Inventors

• Gillis Eric P
• Parcella Kyle E
• Patel Manoj
• Naidu B Narasimhulu

Classifications

• A61K31/5377

  not condensed and containing further heterocyclic rings, e.g. timolol · CPC title

• A61K31/517 Primary

  ortho- or peri-condensed with carbocyclic ring systems, e.g. quinazoline, perimidine · CPC title

• A61P31/18

  for HIV · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title

• C07D405/14

  containing three or more hetero rings · CPC title